Does pulmonary artery denervation improve 6-minute walk distance and reduce clinical worsening compared to bosentan in patients with WHO Group 1 PAH?
Indirect comparison suggests pulmonary artery denervation may provide comparable or greater additive functional benefit versus bosentan in Group 1 PAH, though certainty remains low.
Background: Pulmonary arterial hypertension (PAH) is a progressive vasculopathy characterized by elevated pulmonary vascular resistance (PVR) and eventual right ventricular failure.Current therapy targets 3 endothelial pathways (nitric oxide, prostacyclin, endothelin 1), yet many patients don't achieve low risk status despite combination regimens.Pulmonary artery denervation (PADN) has emerged as a strategy targeting sympathetic overactivity, a proposed 4 th neurohormonal axis, by ablating perivascular sympathetic fibers to reduce vasoconstriction and potentially attenuate vascular remodeling.As no direct RCTs compare PADN with bosentan, comparative effectiveness must rely on indirect evidence synthesis.Methods: Systematic review of WHO Group 1 PAH randomized trials of bosentan vs placebo and PADN vs sham.Bosentan effects were pooled (inverse-variance fixed effect with sensitivity analyses).An anchored indirect comparison (Bucher) linked PADN and bosentan through a common inactive-control node (shamplacebo).Results: 3bosentan placebo-controlled RCTs (N=430) improved 6minute walk distance (6MWD) (MD +34 m, 95% CI 18-50) and reduced clinical worsening (RR 0.27, 95% CI 0.14-0.50;I 2 =0%).In PADN-CFDA (N=128; background PDE-5 inhibitor), PADN improved 6MWD (+33.8 m, 95% CI 16.7-50.9),reduced pulmonary vascular resistance (PVR) (-1.4 WU, 95% CI -2.6 to -0.2), and lowered clinical worsening (OR 0.11, 95% CI 0.01-0.87)at 6 months.Feasibility ultrasound PDN (TROPHY1; N=23) showed PVR -17.8% and 6MWD +42 m without procedure-related serious adverse events.In the add-on network (PADN-CFDA vs COMPASS-2), indirect 6MWD difference favored PADN by +12 m (95% CI -11 to +35).Conclusions: Bosentan provides consistent RCT evidence for improved function and reduced clinical worsening versus placebo.PADN demonstrates sham-controlled hemodynamic and clinical signals on background therapy and may provide comparable or greater additive benefit versus bosentan, but conclusions remain low certainty pending additional blinded PADN trials with longer follow-up
Sampath et al. (Wed,) studied this question.
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